UNITED STATES ENVIRONMENT AL PROTECTION AGENCY WASHINGTON , D

. C

. 20460



## AUG 0 6 2015 OFFICE OF CHEMICAL S A FETY ANO POLLUTION PREVENTION



### MEM O RANDUM

SU B JECT:



### FR O M:

T HR U: EPA's Response to Comments Received on the January 13, 2014, Not i ce of Receipt for Experimental Use Permit 524-EUP-104 (Docket ID Number: EPA-HQ-OPP-2012-0780; FRL-9904

- 99)

Shannon Borges, Lead Bio l ogist

## ~**~ ~**  Microbial Pesticides Branch

### ~**'- ~**  B i opesticides and Pollution Prevention Division (751 lP)**~** Jeannine Kausch , Regu l atory Act i o n Leader Microbial Pesticides Branch Biopesticides and Pollution Preven · John L. Kough, Ph.D., Senior Sc i ent i st 

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# , Microbial Pesticides Branc h Biopesticides and Pollution Prevention ·v i on (751 I P)
Chris A. Wozniak, Ph.D. , Biotechnology Special Assistant 

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,.. . A l an H. Reyno l ds , Lead Biologist / 

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T O : Kimberly Nesci , Chief Microbial Pesticides Branch Biopest i c i des and Po ll ution Prevention Division (7511 P)



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AC KGRO UN D
On March 1 , 2013, the U.S. Environmental Protection Agency (EPA) issued exper i mental u se permit 524

- EUP

- l 04 to Monsanto Company (Monsanto). T h e exper i mental use permit (EUP) allowed Monsanto to conduct testing with plant-incorporated protectant (P I P) corn seed conta i ni n g a double-2 stranded RNA (dsRNA) suppression cassette in combination with several Bacillus thuringiensis ( Bt ) proteins (Cry1A.105, Cry2Ab2, Cry1F, Vip3Aa20, Cry3Bb1, Cry34Ab1, Cry35Ab1, and /or eCry3.1Ab). The testing focused on seed developmen t and increase for future testing (e.g., nursery observations of traits in various backgrounds) and product characterization work (e.g., efficacy and yield benefit evaluations), took place in several states and in the commonwealth of Puerto Rico, and was a uthorized until February 28, 2015. On October 17, 2013, EPA received an application from Monsanto to amend and extend 524

- EUP

- 104. EPA determined that this particular application “may be of re gional or national significance ” ( 40 CFR § 172.11(a) ); therefore, it published a Notice of Receipt in the Federal Register of January 13, 2014 ( 79 FR 2169 ). In re sponse to this publication, EPA received five public commen ts. The public comments and EPA’s response to these comments are presented below.
PUBLIC COMMENTS AND EPA’S RESPONSE
Public Comment #1 http://www.nationofchange.org/monsanto

- s - bt

- toxins

- found

- kill

- human

- embryo

- cells

- 1390666070 BT corn safety needs to be reevaluated NOW! Because a Canadian study shows that it kills embryo cells in pregnant women! EPA’s Response to Public Comment #1 A n anonymous comment received cited a Nation of Change website that listed two articles to support the contention that Cry1Ab proteins enter the bloodst ream, cause kidney damage , and kill human embryos.
Aris and Leblanc (Repro ductive Tox icology, 31:528

– 533, 2011) , the first article, has some important design limitations that question the implications made in the paper about blood levels of Cry1Ab protei n. There is no tracking of the actual diet of the subject women to trace the amount of genetically modified ( GM ) foods consumed , and the use of the enzyme
- linked immunosorbent assay ( ELISA ) detection method has serious flaws. The ELISA method is designed f or use with plant tissue, not human serum, and detects both Cry1Ac and Cry1Ab. While the researchers did use a standard curve based on a purified Cry1Ab protein, the majority of values reported fall outside the range of the standards used to calibrate the ELISA method. There is no statement as to the critical level of detection or level of quan tification for the ELISA method, and this is paramount to make any inference from the results reported considering that the majority of results above non

- detectable a re at or near the lowest standard (1 nanogram Cry1Ab/milliliter ) from the calibration curve. More comments by Mueller and Gorst on the results of the Quebec study , which question its conclusions , are found at Reproductive Toxicology 33:401

– 402 (2012).
Mes nage et al . (Journal of Applied Toxicology 33:695

– 699, 2013) , the second article, reports effects on cell cultures of human embryonic kidney after exposure to Cry1Ab and Cry1Ac to xins and a commercial preparation of Roundup GT Plus. The effects noted relat e to changes in the activity of three enzymes in the Cry1Ab protein and Roundup treatments , and none resulted in cell death. Typically, cytotoxicity is monitored by the viability of the treated cell cultures. The succinate dehydrogenase enzymatic activity effects due to the Cry toxins do not show a dose

- response effect over a six order of magnitude range in the dose administered. The lack of a dose

- response indicates a lack of toxicity. The paper also cites references for previous reports of Cry toxin activ ity on cell cultures. In examining these3 cited reports, the results show cytotoxi c effects on human cancer cells but not normal cells. In addition, the authors of the cited studies are clear that the Bt toxins tested have no insecticidal activity so are probably not related to the insecticidal Cry toxins used in the Mesnage study. While depressed enzymatic activity may be a significant effect, they do not show cytotoxicity or mortality. Since there are f eeding and toxicity studies that show a lack of whole animal effects to the Cry1Ab and Cry1Ac toxins, it is not clear what to infer from these cell culture studies with marginal effects on enzymatic activity.

Public Comment #2 No http://www.nature.com/news/genetically

- modified

- crops - pass - benefits

- to

- weeds

- 1.13517 EPA’s Response to Public Comment #2 Since this anonymous comment does make a scientif ic point or query and references a website that discusses genetically engineered rice (re: gene flow) , EPA did not consider this comment in making a decision on 524

- EUP

- 104, an EUP that involves corn PIPs only.

Public Comments #3, #4, and #5

• We need to stop allowing businesses to produce these chemic als. There is no safe level for pollution. As a business consultant and engineer, I believe that we can have a MUCH healthier economy if we make the polluter pay. Monsanto is CREATING the pollution. You as a resugulator [sic] are approving the pollution. Please stop. Please take a stand.
Terra from Boston

• No, EPA, we the people of the United States of America do not support any form of corporate control of our food supply, national food safety standards, or publicly subsidized land, water, and resources for experimental use of pesticides and GMOs. The corporate model as applied to the fair supply of basic human needs has proven time and time again to have devastating effects on the health of communities lo cal, regional, national and international. Why should we trust companies that produce and use GMO products when they refuse to label their own product? And now the companies that buy, sell and use 100 tons of Roundup in Kauai'i County alone

- not to menti on the 22 tons a year of unregulated, untested, NON

- FDA

- APPROVED EXPERIMENTAL CHEMICALS that are being sprayed within 500 feet of our schools, parks and hospitals

- are suing our county for the right to continue and expand these operations. They can afford to wage this legal war on us because they profit in the hundreds of billions per year at the expense of our water, soil and personal and community health. I urge you to SUMMARILY block Monsanto, who already control 90% of the GMO seed on the planet, fro m further advancing their inhumane plan of monopolizing the food supply, patenting seed and suing farmers out of their land for trying to grow food organically. I promise you, you have the support of the hundreds of millions around the world who have been made aware of the extreme danger of food and chemical corporations governing state and federal law.4 • Monsanto is wrecking [sic] havoc on the environment with their dangerous genetically engineered crops which are failing as we speak! Please deny this permi t! e [sic] plant

- incorporated protectants (PIPs) corn event MON 87411 in combination with single and combined traits against lepidoptera and corn rootworm

. EPA’s Response to Public Comment s #3, #4, and #5 These three comments, two that are anonymous and one from a private citizen, generally expressed opposition to pesticides, pollution, biotechnology, corporations, and/or EPA’s approval of the amendment and extension for 524

- EUP

- 104 . EPA conducted risk and other assessments on the testing program proposed and the PIP active ingredients to be tested. Based upon these scientific assessments, which are available as “Supporting Documents” in this docket (EPA

- HQ

- OPP

- 2012

- 0780), EPA concluded that the active ingre dients to be tested are not expected to cause unreasonable adverse effects to human health or the environment and that the applicant’s limited testing was needed to accumulate information for a Federal, Insecticide, Fungicide, and Rodenticide Act (FIFRA) r egistration. Pursuant to its authority under FIFRA and without further consideration of these comments , EPA therefore proceeded forward with amending and extending 524

- EUP

- 104

.